Molecular Oncology Laboratories, University Department of Medical Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Future Oncol. 2011 Apr;7(4):569-88. doi: 10.2217/fon.11.20.
The growth of new blood vessels (angiogenesis) is critical for tumor growth and progression. The highly conserved Notch signaling pathway is involved in a variety of cell fate decisions and regulates many cellular biological processes, including angiogenesis. Aberrant Notch signaling has also been implicated in tumorigenesis. Notch ligands and receptors are expressed on many different cell types present within the tumor, including tumor cells and the stromal compartment. This article highlights in particular the various mechanisms by which Notch signaling can mediate tumor angiogenesis. The most studied Notch ligands, Delta-like 4 and Jagged1, competitively regulate tumor angiogenesis. Studies have demonstrated that Delta-like 4 functions as a negative regulator of tumor angiogenesis, whereas Jagged1 promotes angiogenesis. Understanding the implications of Notch signaling in various tumor backgrounds will enable the effects of specific Notch signaling inhibition on tumor angiogenesis and growth to be evaluated as a potential for a novel antiangiogenic therapy in the clinic.
新血管的生长（血管生成）对于肿瘤的生长和进展至关重要。高度保守的 Notch 信号通路参与多种细胞命运决定，并调节许多细胞生物学过程，包括血管生成。异常的 Notch 信号也与肿瘤发生有关。Notch 配体和受体在肿瘤内存在的许多不同类型的细胞上表达，包括肿瘤细胞和基质区室。本文特别强调了 Notch 信号可以介导肿瘤血管生成的各种机制。研究最多的 Notch 配体 Delta-like 4 和 Jagged1 竞争性地调节肿瘤血管生成。研究表明，Delta-like 4 作为肿瘤血管生成的负调节剂发挥作用，而 Jagged1 促进血管生成。了解 Notch 信号在各种肿瘤背景下的影响将能够评估特定 Notch 信号抑制对肿瘤血管生成和生长的影响，作为临床新的抗血管生成治疗的潜力。
